Surface proteins of limb cells from 11- to 14-day normal and brachypod mouse embryos have been chemically labeled with diazotized I125-diiodosulfanilic acid and analyzed by SDS- polyacrylamide gel electrophoresis. Eleven-day cells from both normal and mutant embryos exhibit one major glycoprotein with a molecular weight of 220,000 dalton. With cells from 12-day and older normal embryos, the 220,000 component becomes less visible and two other components, 80,000 and 18,000 daltons, become more prominent. The 220,000 component is evident until 14-day of gestation in brachypod cells and the two lower molecular weight components are not visible until 13-days. In other studies, media conditioned by pre-incubation with either 11-, 12- or 13-day formalin-fixed normal or brachypod limb cells had an enhancing effect on in vitro chondrogenesis of both normal and brachypod 12-day limb mesenchyme. The greatest effect appeared to be with media conditioned by 13-day brachypod cells. Investigations of the endogenous levels of cyclic AMP and cyclic GMP during limb chondrogenesis were carried out using the chick mutant, talpid 3, and the mouse mutant, brachypodism. It was observed in normals that a transient rise in cAMP, but not cGMP, occurs just prior to overt chondrogenesis. This rise is less significant in talpid 3 and brachypod limbs.